Cardiac arrhythmias constitute a major source of morbidity and, especially after myocardial infarction, mortality. Our understanding of how antiarrhythmic agents effect conduction velocity, which at the cellular level depends largely on the maximum upstroke velocity (Vmax) of the cardiac action potential, is still incomplete. The present study will evaluate a mechanistic molecular model that accounts for the varying effects of commonly used antiarrhythmic drugs on Vmax in a single, unifying hypothesis. The proposed hypothesis is a quantitative one that predicts the magnitude of the drug effects at different resting potentials, for different driving rates and for premature and late extra systoles. The model predicts the fraction of the Na-channels that are in the available, activated and inactivated states from standard electrophysiological assumptions. Using a set of association and dissociation rate constants for the antiarrhythmic agents with the above three states, it is then possible to compute the effects of these drugs on Vmax at different driving rates, at different membrane potentials and for different rhythm disturbances. The major objectives of this study will be to validate the model and to quantitate the association and dissociation rate constants for the commonly used antiarrhythmic drugs. Preliminary experimental results appear very promising and indicate that this study will substantially improve our basic understanding of antiarrhythmic drugs and will almost certainly result in therapeutically useful information.